Recent studies from this laboratory and others have revealed that several biosynthetic pathways have a common sequence of reactions by which the chain of an alpha-keto acid is lengthened by one carbon. The prototype is the long established case of the formation of alpha- ketoglutarate from oxaloacetate via citrate and isocitrate. Our objective is to explore the scope of this unique mechanism, emphasizing particularly the stereochemistry at each step and the characteristics of each of the enzymes involved. Evidence to date suggests that there may be a common stereochemical pattern despite great diversity of substrate and of enzyme structures. There is some indication that one or more of these enzymic complexes may catalyse repetitive chain-lengthening sequences to produce a whole family of products differing by as much as six or more carbons. While it is possible that this new knowledge may provide direct clues to new therapeutic measures, or to the understanding or diagnosis of metabolic diseases, the essential purpose of the work is to contribute to fundamental knowledge of biochemical mechanisms in living organisms.